Device for receiving a chip shaped carrier and process for assembling a plurality of such devices

ABSTRACT

A device for receiving a chip shaped carrier having an active surface, e.g. a surface which carries an array of DNA oligonucleids and which is adapted to be read by an electro-optical reading device. The device comprises: a cartridge having an opening for receiving a liquid sample and including casing parts ( 14, 15 ); a casing part having an inner surface and outer surface, a first cavity for receiving a chip shaped carrier, and means which provide access to that first cavity and thereby to the active surface of the chip shaped carrier; a sealing material which is at least once reversibly liquidifiable; the shape and dimensions of first cavity, chip shaped carrier, and sealing material, being chosen that the chip shaped carrier fits into the space delimited by the sealing material. The process for mounting the carrier in the cartridge essentially consists in placing the carrier in the first cavity and liquidifying the sealing material. In the liquid state, the sealing material closes any gap between the side walls of the first cavity and the carrier, and after solidification, the sealing material constitutes a strong and liquid-tight bond.

TECHNICAL FIELD

[0001] The present invention relates to a device for receiving a chipshaped carrier having on one side a first surface which includes anactive surface coated with an array of DNA snippets or the like, asecond surface on a second side opposite to said first side, and an edgehaving a peripheral outer surface which extends between said first andsaid second surface, said active surface being adapted to be read by anelectro-optical reading device.

[0002] The invention further relates to an analytical cartridgecomprising a chip receiving device.

[0003] The invention further relates to a process for assembling aplurality of such chip receiving devices.

[0004] The invention further relates to a system for carrying outevaluation and/or monitoring methods involving electro-optical readingof an active surface of a chip shaped carrier.

[0005] The invention further relates to a method for positioning andfastening at least one second object in a first object, the first objectbeing provided with a seat for said at least one second object.

BACKGROUND OF THE INVENTION

[0006] Within the context of the instant invention a chip shaped carrieris a substrate, in particular a glass chip of e.g. squared shape havinga thickness of e.g. 0.7 or 1.0 millimeter and a so called activesurface, which is a surface coated with an array of different snippetsof DNA, e.g. DNA oligonucleotide probes, located at known positions onthat surface. Those snippets of DNA serve as probes for detecting DNAfragments with a complementary DNA sequence.

[0007] Within the context of the instant invention a receiving devicefor receiving such a DNA chip is in particular a one-way cartridge madeof a plastic material, and a cartridge hosting a DNA chip is called ananalytical cartridge.

[0008] DNA chips contained in such cartridges have a wide range ofapplications. For example, they may be used for studying thestructure-activity relationship between different biological materialsor determining the DNA-sequence of an unknown biological material. Forinstance, the DNA-sequence of such unknown material may be determinedby, for example, a process known as sequencing by hybridization. In onemethod of sequencing by hybridization, sequences of diverse materialsare formed at known locations on a surface of a chip, and a solutioncontaining one or more targets to be sequenced is applied to thatsurface. The targets will bind or hybridize with only complementarysequences on the substrate. The locations at which hybridization occursare detected with appropriate detection systems by labeling the targetswith a fluorescent dye, radioactive isotope, enzyme, or other marker.Information about target sequences can be extracted from the dataobtained by such detection systems.

[0009] By combining various available technologies, such asphotolithography and fabrication techniques, substantial progress hasbeen made in the fabrication and placement of diverse materials on chipsof the above mentioned kind. For example, thousands of differentsequences may be fabricated on a single substrate of about 1.28 squarecentimeter in only a small fraction of the time required by conventionalmethods. Such improvements make these substrates practical for use invarious applications, such as biomedical research, clinical diagnostics,and other industrial markets, as well as the emerging field of genomics,which focuses on determining the relationship between genetic sequencesand human physiology.

[0010] As commercialization of such chips becomes widespread, aneconomically feasible device and a method for receiving the chips with ahigh-throughput are desired.

[0011] Since the active surface of the chip, that is the surface thereofwhich is coated with the above mentioned diverse sequences, has to beaccessible e.g. to optical detection means, e.g. in the case offluorescence measurements, the chip has to be inserted into a wall of aone-way cartridge with its active surface facing the interior of theso-called process chamber within the cartridge, and with its oppositesurface being accessible to the optical detection means.

[0012] For instance in the above mentioned method of sequencing byhybridization, processing of the coating on the active surface of thechip includes flooding of the process chamber of the cartridge with asolution containing one or more targets to be sequenced. Therefore, aliquid-tight connection between the chip and the one-way cartridge isnecessary. In a known embodiment described in U.S. Pat. No. 5,945,334this has been achieved under clean-room conditions by attaching the chipto a cavity of the cartridge by means of an adhesive, that is by gluingit into the cartridge. This known method for connecting the chip to thecartridge has serious disadvantages. First, the fluorescence of theadhesives used is so high that it substantially interferes andperturbates fluorescence measurements performed on the active surface ofthe chips and can even have saturating effect on a photomultiplier usedfor performing the fluorescence measurements. The adhesive has to beapplied by a dispenser, which is not possible with any adhesive.Furthermore, the known adhesives are prone to develop or contain gases,which when freed would disturb the reactions. Another problem isoccasioned by solvent present in the adhesive because the solvent mayreact with the DNA samples on the active surface. It has even be foundthat solvent negatively influence the properties of the glass surface ofa chip shaped carrier, e.g. blurs it.

[0013] A further disadvantage of the known method for connecting thechip to the cartridge is that it is performed manually and is notsuitable for being performed by automated means, because a very carefulpositioning within the receiving window of the cartridge is necessary.Furthermore, as the adhesive is applied thereafter, a second control, ifthe DNA chip is still in place, has to be performed. These operationsare aggravated by the relatively large tolerances of the dimensions ofthe chips and their rather uneven edges.

BRIEF SUMMARY OF THE INVENTION

[0014] A first aim of the invention is therefore to provide a device forreceiving a chip of the above mentioned kind which avoids at least oneof the above-mentioned disadvantages, and preferably all of it.

[0015] A second aim of the invention is to provide an analyticalcartridge comprising a chip receiving device according to the invention.

[0016] A third aim of the invention is to provide a process forassembling a plurality of chip receiving devices according to theinvention with a high throughput.

[0017] A fourth aim of the invention is to provide a system for carryingout evaluation and/or monitoring methods involving electro-opticalreading of an active surface of a chip shaped carrier with avoiding atleast one of the above mentioned disadvantages of prior art embodiments.

[0018] A fifth aim of the present invention is to provide a method formore conveniently placing a first object in a second object and tofasten it there.

[0019] According to the invention the above-mentioned first aim isattained with a device for receiving a chip shaped carrier having on oneside a first surface which includes an active surface coated with anarray of DNA snippets or the like, a second surface on a second sideopposite to said first side, and an edge having a peripheral outersurface which extends between said first and said second surface, saidfirst surface being adapted to be read by an electro-optical readingdevice, said device comprising

[0020] (a) a cartridge having an opening for introducing a liquid sampleinto said cartridge,

[0021] (b) said cartridge having a casing part which has an outersurface and an inner surface, a first cavity for receiving a chip shapedcarrier,

[0022] (c) a layer of a sealing material which is reversiblytransformable at least once from a solid state into a fluid state andwhich is provided in a sufficient amount to establish a liquid-tightbond between the inner surface of side walls of the first cavity andsaid peripheral outer surface of the edge of the chip shaped carrierwhen the latter is placed into said first cavity.

[0023] The main advantages of a chip receiving device according to theinvention are due to the fact that the required liquid-tight connectionof the chip to the cartridge is achieved by means of a solid sealingmaterial which liquidifies when heated over a certain temperature andresolidifies when cooled. In the solid state, the sealing materialconstitutes a substantial part of the wall of a seat for a chip formedwithin the cartridge and thereby contributes to define the position ofthe chip when it is set in the socket. After the chip is positioned inthe seat, the sealing material is liquidified by heating it and thenfills the space between the solid walls of the seat and the chip. Sincethis happens when the sealing material is in liquid state, anyirregularity of the edges of the chip does not impair the quality of thesealing.

[0024] Surprisingly, depending on the nature of the sealing material,the chip remains fluid-tight even if a sensible overpressure is applied,e.g. exerted by a liquid filled in the chamber of the cartridge.

[0025] A preferred sealing material is a material which is apt to bemolten by applying heat and which resolidifies when cooled. A preferredsealing material is a hotmelt material, particularly a hotmelt adhesive,i.e. an adhesive fusible by heat, also known as “thermoplasticadhesive”.

[0026] According to the invention the above mentioned second aim isattained with an analytical cartridge which comprises a chip shapedcarrier inserted in the first cavity of a chip receiving deviceaccording to the invention, wherein the sealing material fills theclearance between the walls of the first cavity and the chip.

[0027] According to the invention the above mentioned third aim isattained with a process for assembling a plurality of analyticalcartridges according to the invention, which process comprises:

[0028] (a) providing a plurality of casing parts to an automatedassembly line,

[0029] (b) providing a plurality of chip shaped carriers having each anactive surface to said assembly line,

[0030] (c) positioning each of said chip shaped carriers within thefirst cavity of one of said casing parts by means of a first automaticapparatus,

[0031] (d) bonding each of said chip shaped carriers in said firstcavity of said casing part, by liquidifying the sealing material.

[0032] The main advantages of a process according to the invention forassembling a plurality of chip receiving devices having the structureproposed by the instant invention are that such a process is adapted tobe entirely performed using standard automated means and provides a highthroughput.

[0033] According to the invention the above mentioned fourth aim isattained with a system for carrying out evaluation and/or monitoringmethods involving electro-optical reading of an active surface of a chipshaped carrier, said system comprising

[0034] (a) a cartridge having an opening for introducing a liquid sampleinto said cartridge, and a casing part,

[0035] (a.1) said casing part being comprised in the cartridge andhaving an inner surface and an outer surface, a first cavity forreceiving a chip shaped carrier, and means which provide access to afirst cavity and thereby to said active surface of said chip shapedcarrier, and

[0036] (a.2) said first cavity having a flat bottom surface and sidewall surfaces which extend between said inner surface of said casingpart and said bottom surface;

[0037] (b) a sealing material being provided in said first cavity, saidsealing material consisting of an at least once reversibly liquidifiablematerial, and

[0038] (c) a chip shaped carrier having an active surface which isadapted to be read by an electro-optical reading device, said chipshaped carrier being positioned in said first cavity of said casingpart, and the sealing material filling the gap between the cavity walls,particularly its side walls, and the chip shaped carrier in order tohold the chip shaped carrier firmly and fluid-tightly in the cavity.

[0039] The main advantage of a system according to the invention is thatit makes possible to carry out evaluation and/or monitoring methodsinvolving electro-optical readings of an active surface of a chip shapedcarrier of the above mentioned type and eliminates the above mentioneddrawbacks of prior art equipment.

[0040] According to the invention the above mentioned fifth aim isattained with a method for positioning and fastening at least one secondobject in a first object, the first object being provided with a seatfor the second objects, said method comprising

[0041] forming at least part of the walls of the seat, preferably thecircumferential rim, from a solid material which is at least oncereversibly liquidifiable, preferably a hot melt material,

[0042] placing the second objects into the seat, and

[0043] liquidifying the solid liquidifiable material so that the lattermaterial attaches the first object to the second object and afterresolidification establishes a bond between the first object and thesecond object.

[0044] According to this more general aspect of the invention, by use ofhotmelt material, it is possible to produce solid objects providingseats, frames, cavities or the like, with the intention to place thereinone or also more than objects and to readily fasten them therein. Forthis purpose, the rim of the seat is constituted at least to asufficient part by a hot melt material. As the hot melt is solid undernormal conditions, it is apt to be quite exactly adapted to the geometryof the second object(s), and the latter when placed into the seat, areexactly registered therein. Thereby, an additional control of exactposition of the second object may be waived. After placing the secondobject(s) into the respective seat, the solid hotmelt is locally heatedin order to render it liquid and to fasten the second object(s) in theirseat.

[0045] Particularly advantageous is that the first object and the partsmade of hot melt may be manufactured long time before they are used toreceive and hold the second object(s). In other words, the hot melt, ormore generally, the material which liquidifies when heated over acertain temperature and resolidifies again when cooled, is a solid partwhich is formed on the first object before it is used to form a bondbetween the second and the first object and which is molten, e.g. byirradiation using laser light, to behave as a glue and/or a fluidsealing material.

[0046] Preferred exemplary embodiments of the invention are describedhereinafter more in detail with reference to the accompanying drawings,wherein

BRIEF DESCRIPTION OF DRAWINGS

[0047]FIG. 1 shows a perspective view of a chip receiving devicecomprising a cartridge 12;

[0048]FIG. 2 shows a cross-sectional, exploded view of means usedaccording to the invention for attaching a chip shaped carrier 21 to afirst casing 14 which is part of a cartridge 12;

[0049]FIG. 3 shows the same as FIG. 2, but with a chip inserted andenergy sources;

[0050]FIG. 4 shows a cross-sectional view of the means represented inFIG. 2 after they have been assembled according to the invention;

[0051]FIG. 5 shows a top view of the assembly represented in FIG. 4;

[0052]FIG. 6 shows a schematic partial cross-section of a cartridge, and

[0053]FIG. 7 shows an assembly line for automatically receiving chips incartridges.

LIST OF REFERENCE NUMBERS

[0054] 12 cartridge 13 opening (for introduction of liquid) 14 firstcasing part 15 second casing part 16 outer surface of casing part 14 17inner surface of casing part 14 18 first cavity of casing part 14 20joint clearance 21 chip (shaped carrier) 22 second cavity of casing part14 23 bottom surface of first cavity 18 24 side wall surfaces of firstcavity 18 25 opening in 23 26 hotmelt 28 active surface (part of firstsurface 61 covered by probe array 32) 29 inner surface of hotmelt 26 30laser light 31 edge of chip 21 32 probe array on first surface of chipshaped carrier 21 33 processing chamber 41 stock of casing parts 14, 1542 first conveyor 43 die-bonder 44 second conveyor (blue tapes) 46 diecollet on 53 47 laser welding machine 48 automatic packaging apparatus49 stock of assembled cartridges 12 51 electro-optical reading system 52working frame of 43 53 tool holder of 43 61 first surface of 21 62second surface of 21 63 third surface of 21 70 side length of chip 21 71side length of active surface 28 on chip 21 73 thickness of chip 21

DESCRIPTION OF PREFERRED EMBODIMENTS

[0055] As shown by FIG. 1, a chip receiving device according to theinvention comprises a cartridge 12. Cartridge 12 comprises a firstcasing part 14 and a second casing part 15. Casing part 15 has anopening 13 for introducing a liquid sample into cartridge 12. Casingpart 15 is preferably made of an optically non-transparent material.

[0056] As can be appreciated from FIG. 2, casing part 14 has an outersurface 16 and inner surface 17, a first cavity 18 for receiving a chipshaped carrier 21—called for simplicity chip 21 hereinafter—and a secondcavity 22 which forms a window providing access to said first cavity 18and thereby to the active surface 28 of chip shaped carrier 21. Thisstructure is just one example of means which provide visual access toactive surface 28.

[0057] Typically, chip 21 is made of glass, has a thickness of 0.7 or1.0 millimeter, and has substantially the shape of a square. Since thesize of chip 21 has a relatively high dimensional tolerance of e.g.0.0762 millimeter of length and width, in the embodiment describedhereinafter the space available in cavity 18 for receiving andpositioning chip 21 has a corresponding joint clearance 20 (cf. FIG. 6).

[0058] Chip 21 has a first surface 61 a part of which is an activesurface 28 which is covered by oligonucleotide probes 32 and which mustnot be touched at all to avoid any damage of the probes 32.

[0059] Chip 21 has a second surface 62 opposite to first surface 61 andan edge having a peripheral surface 63 which extends between the firstsurface 61 and the opposite surface 62 of chip 21.

[0060] Cavity 18 has a flat bottom surface 23 and side wall surfaces 24which extend between outer surface 16 of casing 14 and bottom surface23. As shown by FIGS. 2-6, a layer of a solid sealing hotmelt material26 is arranged on side wall surfaces 24. The solid hotmelt is fusible byheating, specifically by irradiation with laser light, and solidifiesagain when cooled. In order to facilitate the insertion of the chip 21,the inner surfaces 29 of the hotmelt material layer 26 may be inclinedso that an opening tapering to the bottom surface 23 is obtained. Forthis purpose, the tapering caused by injection molding of this piece maysuffice.

[0061] The bottom surface 23 has an opening 25 which opens into secondcavity 22.

[0062] As can be appreciated from FIGS. 2 and 3, chip 21 is positionedin cavity 18 of casing part 14. The hotmelt 26 is heated by means oflaser light 30 provided by a suitable light source. The laser light isdirected sequentially to a number of points of hotmelt material layer 26or simultaneously to the whole hotmelt material layer 26. The heatedhotmelt 26 becomes then fluid and fills the clearance 20 between walls24 and the edge of the chip 21. Obviously, irregularities in the shapeof the edge 31 of the chip 21 do not have any sensible influence on thisprocess, neither on the quality of the bond between the hotmelt 26 andthe chip 21. Just on the contrary, it can be expected thatirregularities ameliorate its mechanical strength.

[0063] Further advantages are:

[0064] a) there is no mechanical stress involved in establishing thebond between casing 14 and chip 21 in contrast to known devices wherethe chip is held by clamping means;

[0065] b) no adhesive has to be administered after positioning the chip,and the disadvantage of the known adhesives set forth in theintroduction are avoided;

[0066] c) the chip may be inserted from the outer surface of the housingpart 14;

[0067] d) solidification of the hotmelt, i.e. the bonding process, is aphysical process (phase transition), and quite fast;

[0068] e) the hot melt material may preferably be chosen such that itretains permanently a certain elasticity;

[0069] f) the hotmelt material does not impair fluorescencemeasurements, i.e. has low fluorescence activity at 633 nm; and

[0070] g) increased life time with respect to conventional adhesives.

[0071] In one embodiment, the following materials were used:

[0072] Chip 21: glass

[0073] Hotmelt layer 26: Ecomelt P1 Ex318 (Collano Ebnöther AG,Schweiz): Softening temperature: 90° C. (DIN 52011; ASTM D36/E28);working temperature range: 150-180° C., typically 160° C.;

[0074] Casing 14 respectively 15: Topas 6013 (Ticona GmbH, Deutschland):a copolymer of ethylene and nobornene, more generally a cycloolefiniccopolymer (COC); shape heat resistance temperature: 130° C.

[0075] It was found that the chip was safely held against anoverpressure of 500 mbar at 20° C., and no leakage occurred. Even at 60°C., the joint withstood the pressure for some minutes. Failure at 300mbar overpressure, which regularly occurs in normal operation, istherefore excluded.

[0076]FIGS. 4 and 5 show the fixed state in a cross-sectional and a topview, respectively. Particularly in FIG. 4, it is evident that thehotmelt 26 has filled up the clearance 20 from the bottom.

[0077] As can be appreciated from FIGS. 2 to 5, the shape and dimensionsof cavity 18, chip 21, hotmelt layer 26 and opening 25 of bottom surface23 of cavity 18 are so chosen that the chip 21 fits into the spacedelimited by the hotmelt layer 26.

[0078] In a preferred embodiment part of which is schematically shown byFIG. 6, chip 21 has a first surface 61 a part of which is an activesurface 28 coated with a so called probe array 32, i.e. an array ofdiverse sequences, e.g. DNA oligonucleotides, located at known positionson that first surface 61, and a second surface 62 opposite to said firstsurface. A third surface 63 which extends between said first and secondsurfaces, is normal to these surfaces, and is the outer surface of thelateral periphery or edge of chip 21.

[0079] Since the probe array 32 of chip 21 has to be accessible e.g. tooptical detection means, e.g. for performing fluorescence measurements,chip 21 is inserted into the outer wall of cartridge 12, and its firstsurface 61 with the probe array 32 on it faces the interior of aso-called process chamber 33 within cartridge 12.

[0080] The geometric specifications of mounting of chip 21 arerepresented in FIG. 6, with all dimensions are indicated in millimeters.As indicated therein, a chip 21 may usually have three sizes designatedby numbers 100, 169 and 400 and is substantially quadratic in shape.Chip size 100 has a side length 70 of 10.92 millimeters. Chip size 169has a side length 70 of 8.153 millimeters. Chip size 400 has a sidelength 70 of 5.384 millimeters. The active surface of chip size 100 hasa side length 71 of 9.5 millimeters. The active surface of chip 21 size169 has a side length 71 of 6.73 millimeters. The active surface of chipsize 400 has a side length 71 of 3.96 millimeters. Thickness 73 of thechip 21 is about 0.7 mm.

[0081] A further aspect of the invention relates to a process for anautomated assembly of a plurality of chip receiving devices according tothe invention.

[0082]FIG. 7 schematically shows the structure of a completely automaticassembly line for carrying out such a process. This assembly linecomprises a stock 41 of casing parts 14, 15 of cartridges 12, a firstconveyor 42, a die bonder 43, a second conveyor 44 for conveying bluetapes which come from a diamond saw cutting machine and which carry aplurality of chip shaped carriers 21, a laser welding machine 47, anautomatic packaging apparatus 48, and a stock of completely assembledchip receiving devices 49. Assembly line components 42 to 48 are allstandard apparatuses and devices suitable for automated operation. Diebonder 43 comprises a blue tape support 45 having an expansionmechanism, a working frame 52 movable in x- and y-direction and a toolholder 53 which holds a die collet 46. Tool holder 53 is connected toworking frame 52 and is thereby movable in x- and y-direction. Toolholder 53 has a means, e.g. a spindle, which enables to move die collet46 in z-direction.

[0083] According to the invention, a process for assembling a pluralityof analytical cartridges comprising cartridges 12 comprises thefollowing steps:

[0084] (a) providing to an input side of the automatic assembly lineshown by FIG. 7 a plurality of casings 14, each of the casings 14comprising a hotmelt layer 26 as described above,

[0085] (b) providing a plurality of chip shaped carriers 21 each ofwhich has an active surface 28 to said assembly line,

[0086] (c) positioning each of the carriers 21 within the cavity 18 ofone of said casing parts 14 by means of automatic die bonder 43,

[0087] (d) melting the hotmelt layer 26 in the laser welding machine 47in order to have the liquidified hotmelt material fill the clearance 20between side walls 24 and the edge 63 of the chip 21.

[0088] In the above mentioned process steps (a) and (b), casings 14 arepreferably transferred one-by-one via first conveyor 42 from the stockof parts 41 to die bonder 43 and from there successively to the otherparts of the assembly line where a processing step has to be carriedout. In a similar way and with a proper timing, chip shaped carriers 21are also transferred one-by-one via second conveyor 44 and blue tapesupport 45 to the die bonder 43.

[0089] In all above mentioned process steps, the active surface 28 ofchip 21 and particularly the probes 32 thereon are not touched at all,and this ensures that no damage of that active surface can take placeduring the assembling process. In addition, the above defined processensures that the quality of the cutting of chip 21 remains basicallyunchanged.

[0090] In a further preferred embodiment, at least the following of theabove mentioned assembling steps are carried out in a clean room:

[0091] positioning each of said carriers 21 within cavity 18, and

[0092] melting of the hotmelt 26.

[0093] After bonding of a chip 21 to a casing part 14, this casing partand a complementary casing part 15 are forwarded to an automaticpackaging apparatus 48, where they are put together to form a completechip receiving device, that is a cartridge 12 containing a chip shapedcarrier 21.

[0094] An outstanding advantage of the device and the assembling processaccording to the invention is that they allow adjustment of the lateralinsertion clearance when inserting the chip in cavity 18 of casing part14. This adjustment possibility eliminates on the one hand the need fora highly accurate positioning of chip 21 for mounting it and the needfor relatively large forces for effecting that mounting, and on theother hand allows the use of commercially available standard appliancesfor the automated manufacture of integrated circuits.

[0095] An example of such a standard appliance is e.g. a die bonderwhich can supply a maximum joining force of 10 Newton. A die bonder istypically used for bonding an electronic silicon chip on a so-calledlead frame.

[0096] The advantage of such an automated assembly line is that it makespossible to use a mounting machine suitable for use in a clean-room,namely the die bonder, in which the removal of chip 21 from a so-called“blue tape” is already integrated. The minimization of the joining forceused for bonding chip 21 and casing part 14 is supported by a videosystem.

[0097] According to the invention a system for carrying out evaluationand/or monitoring methods involving electro-optical reading of an activesurface 28 of a chip shaped carrier 21 comprises

[0098] (a) a cartridge 12 having an opening 13 for introducing a liquidsample into said cartridge 12,

[0099] (b) a casing part 14 comprised in cartridge 12, which has

[0100] (b.1) an outer surface 16 and inner surface 17,

[0101] (b.2) a first cavity 18 for receiving a chip shaped carrier 21,

[0102] (b.3) means 22 which provide an access to the first cavity 18 andthereby to an active surface 28 of chip shaped carrier 21, wherein

[0103] (b.4) the first cavity 18 has a flat bottom surface 23 and sidewall surfaces 24 which extend between said outer surface 16 of saidcasing part 14 and said. bottom surface 23,

[0104] (c) a hotmelt layer 26 applied to the side walls 24 of the firstcavity 18, wherein the inner walls 29 optionally form an obtuse anglewith that bottom surface 23 so that the cavity 18 widens with increasingdistance from the bottom surface 23,

[0105] (d) a chip shaped carrier 21 having an active surface 28 which isadapted to be read by an electro-optical reading device, and beingpositioned in the first cavity 18 of casing part 14,

[0106] (e) the shape and dimensions of first cavity 18, chip shapedcarrier 21, and hot melt 26 being such that a chip shaped carrier 21fits into the space delimited by said hotmelt layer 26.

[0107] In a preferred embodiment, the above described system furthercomprises electro-optically reading means 51, schematically representedin FIG. 6, for reading the probe array 32 of chip shaped carrier 21.Electro-optical reading means 51 is e.g. a fluorometer, i.e. anapparatus comprising a light source for irradiating active surface 28with an excitation beam, light detection means for detecting fluorescentlight emitted by the probe array 32 on the active surface 28 andproviding a corresponding output signal and means for evaluating and/ormonitoring that output signal.

[0108] Modifications and alternative embodiments of the invention willbe apparent to those skilled in the art in view of the foregoingdescription. Accordingly, this description is to be construed asillustrative only and is for the purpose of teaching those skilled inthe art the best mode of carrying out the invention. Details of theapparatus and the processes described above may be varied withoutdeparting from the spirit of the invention and the exclusive use of allmodifications which come within the scope of the appended claims isreserved. Possible modifications within the scope of the inventions areas follows:

[0109] The chip may be made of other material than glass according tothe requirements imposed by the observation and/or analyzing techniqueof the active surface area of the chip, pressure conditions in use,chemical stability and so on.

[0110] Other sealing materials which liquidify when heated may beconsidered. However, from the present empirical knowledge, a material ispreferred, which is essentially solvent free.

[0111] Instead of laser light, another energy source maybe used,preferably one, the energy of which may be concentrated on the hotmeltmaterial in order not to affect the chip, and in particular the probearray on the active surface. However, the heating, i.e. the energysupply has to be controlled in order to avoid heating the material to anextent that it begins to decompose. Decomposition may not onlydeteriorate the properties of the sealing material, but also producereactive, possibly volatile molecules which may attack the DNA probes.The same applies, of course, to the material of the housing, as far asit is exposed to the energy source. Preferably an energy source shouldbe used which is apt to be exactly focused, like a laser, so that aheating of the surrounding casing can be perfectly avoided. In apreferred embodiment ultrasonic waves are used for heating the hotmeltmaterial 26. This energy form has the advantage that the process can becarried out in shorter time.

[0112] It is not necessary that the solid hotmelt material 26 perfectlycovers the entire surface of the side walls of the cavity 18. Any gapswill then be closed when the hotmelt material liquifies during thebonding process.

[0113] The cartridge may be made of another material, preferably apolymeric material, which is inert under the condition of the reactionor reactions to be performed in the analytical cartridge.

[0114] Although preferred embodiments of the invention have beendescribed above using specific terms, such description is forillustrative purposes only, and it is to be understood that changes andvariations may be made without departing from the spirit or scope of thefollowing claims.

What is claimed:
 1. A method for positioning and fastening a second object in a first object, the first object being provided with a seat for said at least one second object, both objects being made of a non-metallic materials, said method comprising forming at least part of the walls of the seat, preferably the circumferential rim, from a liquidifiable solid material which is at least once reversibly liquidifiable by heating it, said solid material being other than said non-metallic materials, placing the second objects into the seat, liquidifying said solid material by heating it so that the latter material attaches the first object to the second object, and allowing said liquidifiable material to cool and resolidify, said liquidifiable material thereby forming a bond between the first object and the second object.
 2. A method according to claim 1, wherein said solid material is a hotmelt material.
 3. A method according to claim 1, wherein said first object is made of glass.
 4. A method according to claim 1, wherein said second object is made of a plastic material.
 5. The method according to claim 1, wherein heat is applied to said liquidifiable solid material locally and essentially sequentially at all sites where a bond between the first object and the second object is to be attained, preferably by using laser light. 